Aromatic hydroxylation and sulfation of phenazopyridine by Cunninghamella echinulata

1991 ◽  
Vol 37 (7) ◽  
pp. 504-508 ◽  
Author(s):  
Brian C. Foster ◽  
Barry H. Thomas ◽  
Jiri Zamecnik ◽  
Brian A. Dawson ◽  
D. Lynden Wilson ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Mass Spectrum ◽  
Filamentous Fungus ◽  
Hplc Analysis ◽  
Parent Drug ◽  
Inhibitory Effects ◽  
Cunninghamella Echinulata ◽  
Aromatic Hydroxylation ◽  
Metabolic Products ◽  
Sulfate Conjugate

The metabolism of phenazopyridine was studied in the filamentous fungus Cunninghamella echinulata (synonym C. bainieri) ATCC 9244. Metabolic products were initially isolated by HPLC and TLC, with further characterization achieved by a combination of GLC, NMR, mass spectrum (MS), and GC–MS analyses. Selected samples of the incubation broths were treated with (β-glucuronidase–arylsulfatase. In addition to the reported mammalian metabolites p-aminophenol, acetaminophen, 2′-hydroxyphenazopyridine, 4′-hydroxyphenazopyridine, and parent drug, a novel metabolite was unequivocally identified as the sulfate monoester of 4′-hydroxyphenazopyridine.para-Hydroxylation of the aromatic ring with subsequent sulfoconjugation were observed as the major routes of metabolism. Ethanol, carbon monoxide, and quinidine had inhibitory effects on the C. echinulata metabolism of phenazopyridine, suppressing formation of 4′-hydroxyphenazopyridine and its sulfate monoester. Key words: Cunninghamella echinulata, biotransformation, GLC analysis of phenazopyridine, HPLC analysis of phenazopyridine, phenazopyridine, sulfate conjugate.

scholarly journals Ruthenium, Not Carbon Monoxide, Inhibits the Procoagulant Activity of Atheris, Echis, and Pseudonaja Venoms

2020 ◽  
Vol 21 (8) ◽  
pp. 2970 ◽  
Author(s):  
Vance G. Nielsen
Keyword(s):  
Carbon Monoxide ◽  
Phospholipase A2 ◽  
Procoagulant Activity ◽  
Inhibitory Effects ◽  
Snake Venoms ◽  
Radical Intermediate ◽  
Experimental Systems ◽  
Phospholipase A2 Activity

The demonstration that carbon monoxide releasing molecules (CORMs) affect experimental systems by the release of carbon monoxide, and not via the interaction of the inactivated CORM, has been an accepted paradigm for decades. However, it has recently been documented that a radical intermediate formed during carbon monoxide release from ruthenium (Ru)-based CORM (CORM-2) interacts with histidine and can inactivate bee phospholipase A2 activity. Using a thrombelastographic based paradigm to assess procoagulant activity in human plasma, this study tested the hypothesis that a Ru-based radical and not carbon monoxide was responsible for CORM-2 mediated inhibition of Atheris, Echis, and Pseudonaja species snake venoms. Assessment of the inhibitory effects of ruthenium chloride (RuCl3) on snake venom activity was also determined. CORM-2 mediated inhibition of the three venoms was found to be independent of carbon monoxide release, as the presence of histidine-rich albumin abrogated CORM-2 inhibition. Exposure to RuCl3 had little effect on Atheris venom activity, but Echis and Pseudonaja venom had procoagulant activity significantly reduced. In conclusion, a Ru-based radical and ion inhibited procoagulant snake venoms, not carbon monoxide. These data continue to add to our mechanistic understanding of how Ru-based molecules can modulate hemotoxic venoms, and these results can serve as a rationale to focus on perhaps other, complementary compounds containing Ru as antivenom agents in vitro and, ultimately, in vivo.

Noradrenaline and normetadrenaline metabolism in portal cirrhosis

1964 ◽  
Vol 207 (5) ◽  
pp. 1087-1094 ◽  
Author(s):  
McC. Goodall ◽  
Harold Alton ◽  
Martha Henry
Keyword(s):  
Monoamine Oxidase ◽  
Alcoholic Cirrhosis ◽  
Transferase Activity ◽  
Monoamine Oxidase Activity ◽  
Noradrenaline Metabolism ◽  
Portal Cirrhosis ◽  
Indwelling Catheter ◽  
Methyl Transferase ◽  
Metabolic Products ◽  
Sulfate Conjugate

Four patients with moderate to severe portal (alcoholic) cirrhosis were injected intravenously with dl-noradrenaline-2-C14. Urine was collected via an indwelling catheter at 10-min intervals for 1 hr and thereafter for 6 and 24 hr. The metabolic products of noradrenaline were separated, identified, and their radioactivity measured. The same subjects were also injected with dl-normetadrenaline-1-C14, the O-methylated metabolic product of noradrenaline, and the urine samples similarly processed. The results seem to indicate that in portal cirrhosis noradrenaline metabolism is altered. In the period immediately following the injection of noradrenaline there is a slight decrease in the catechol-O-methyl transferase activity but thereafter it is either unchanged or slightly increased. Further, the cirrhotic shows a distinct predilection for conjugating both noradrenaline and normetadrenaline. This is reflected by a significant increase in the sulfate conjugate of both of these compounds. The monoamine oxidase activity is decreased slightly throughout the collection periods. This is reflected by a decrease in the formation of 3-methoxy-4-hydroxymandelic acid following an injection of both noradrenaline and normetadrenaline.

The pharmacokinetics (PK) and pharmacodynamics (PD) of ABT-751 in children with recurrent neuroblastoma or other solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9557-9557
Author(s):  
E. Fox ◽  
B. C. Widemann ◽  
J. M. Maris ◽  
S. L. Cohn ◽  
H. Xiong ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase 1 ◽  
Parent Drug ◽  
Molar Ratio ◽  
Primary Metabolite ◽  
Drug Concentrations ◽  
Apparent Clearance ◽  
Major Route ◽  
Microtubule Formation ◽  
Sulfate Conjugate

9557 Background: ABT-751 is an orally administered agent that binds to the colchicine site on β-tubulin and blocks microtubule formation. We studied the PK and PD of ABT-751 and its sulfate and glucuronide conjugates in children enrolled on a phase 1 trial in solid tumors and a pilot study in neuroblastoma. Methods: Seventy-two children (2–18 yrs) received ABT-751 on a once, daily × 7d or daily × 21d schedule. Sixty had PK plasma sampling (53 sets analyzed), and 41 had a 24h urine collection after the first dose. Drug concentrations were quantified with a LC/MS/MS assay. Results: Median (range) plasma PK parameters are shown in the table . ABT-751 was rapidly absorbed (Tmax , 2h), and the Cmax and AUC0-8 increased in proportion to dose. The median molar ratio of the sulfate plasma AUC0-8 to glucuronide plasma AUC0-8 was 1.5. The median (range) percent of the administered dose excreted in urine as ABT-751, glucuronide, or sulfate conjugates was 0.09 (0–0.4)%, 10.2 (1.0–38.5)%, and 12.6 (2.3–50.9)%, respectively. The median ABT-751 AUC0-8 was higher in patients with dose-limiting toxicity (DLT) compared to those without DLT on the 7d (118 vs. 74.5 μg·h/mL; P=0.014) and 21d (73.8 vs 49.3 μg·h/mL; P=0.049) schedules. In 28 patients with neuroblastoma, the AUC0-8 did not correlate with time to progression. Apparent clearance (CL/F) did not correlate with age or gender. Conclusions: PK samples were obtained from 83% (60/72) of children enrolled. The ABT-751 AUC0-8 was dose proportional; inter- and intra-patient variability was low. Patients who experienced DLT had higher ABT-751 AUC0-8. The mean CL/F of ABT-751 was similar to that observed in adults (40 mL/min/m2) but did not correlate with age or gender. The sulfate conjugate was the primary metabolite in plasma and urine. Urinary excretion was not a major route of elimination of the parent drug. [Table: see text] No significant financial relationships to disclose.

Metabolomics of the recovery of the filamentous fungus Cunninghamella echinulata exposed to tributyltin

2018 ◽  
Vol 127 ◽  
pp. 130-138 ◽  
Author(s):  
Adrian Soboń ◽  
Rafał Szewczyk ◽  
Sylwia Różalska ◽  
Jerzy Długoński
Keyword(s):  
Filamentous Fungus ◽  
Cunninghamella Echinulata

Microbial detoxification of carvedilol, a β-adrenergic antagonist, by the filamentous fungus Cunninghamella echinulata

Chemosphere ◽  
2017 ◽  
Vol 183 ◽  
pp. 18-26 ◽  
Author(s):  
Katarzyna Zawadzka ◽  
Przemysław Bernat ◽  
Aleksandra Felczak ◽  
Katarzyna Lisowska
Keyword(s):  
Filamentous Fungus ◽  
Cunninghamella Echinulata ◽  
Adrenergic Antagonist ◽  
Microbial Detoxification

α-Glucosidase Inhibitory Compounds in Malus Halliana Koehne Tea

2017 ◽  
Vol 17 (3) ◽  
pp. 236-241 ◽  
Author(s):  
Feng Fajin ◽  
Yin Zhenhua ◽  
Wang Pengyu ◽  
Zhang Qianjun ◽  
Kang Wenyi
Keyword(s):  
Mass Spectrum ◽  
Inhibitory Activity ◽  
Positive Control ◽  
Inhibitory Effects ◽  
Butanol Extract ◽  
Nmr Data ◽  
Inhibitory Compounds ◽  
First Time ◽  
Better Than ◽  
C Nmr

The aim of this study was to isolate α-glucosidase inhibitory constituents from Malus halliana Koehne tea. The ethyl acetate and n-butanol extract of M. halliana tea showed α-glycosidase inhibitory activity (IC50 332.24 and 168.92 μg/mL, respectively) and eleven compounds (1–11) were isolated and identified by extensive NMR data (1H and 13C NMR) and mass spectrum. Eleven compounds were isolated from this plant for the first time, and compounds 2, 4, 5, 7 and 8 were isolated from the genus for the first time. The α-glucosidase inhibitory activity of compounds 6, 8, 9 and 10 (IC50 6.32, 15.53, 37.68 and 7.87 μM) were better than that of other compounds (IC50 > 200 μM). Compounds 1~5 and 11 displayed moderate inhibitory effects on α-glucosidase, with IC50 values of 226.76~435.56 μM, whereas compound 7 (IC50 3246.17 μM) was inactive, and lower than that of acarbose as positive control (IC50 1819.72 μM).

Amsorb 

1999 ◽  
Vol 91 (5) ◽  
pp. 1342-1342 ◽  
Author(s):  
James M. Murray ◽  
Craig W. Renfrew ◽  
Amit Bedi ◽  
Conor B. McCrystal ◽  
David S. Jones ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Carbon Monoxide ◽  
Parent Drug ◽  
Soda Lime ◽  
Calcium Sulphate ◽  
Carbon Dioxide Absorption ◽  
Compound A ◽  
New Material ◽  
Carbon Dioxide Absorbent

Background This article describes a carbon dioxide absorbent for use in anesthesia. The absorbent consists of calcium hydroxide with a compatible humectant, namely, calcium chloride. The absorbent mixture does not contain sodium or potassium hydroxide but includes two setting agents (calcium sulphate and polyvinylpyrrolidine) to improve hardness and porosity. Methods The resultant mixture was formulated and subjected to standardized tests for hardness, porosity, and carbon dioxide absorption. Additionally, the new absorbent was exposed in vitro to sevoflurane, desflurane, isoflurane, and enflurane to determine whether these anesthetics were degraded to either compound A or carbon monoxide. The performance data and inertness of the absorbent were compared with two currently available brands of soda lime: Intersorb (Intersurgical Ltd., Berkshire, United Kingdom) and Dragersorb (Drager, Lubeck, Germany). Results The new carbon dioxide absorbent conformed to United States Pharmacopeia specifications in terms of carbon dioxide absorption, granule hardness, and porosity. When the new material was exposed to sevoflurane (2%) in oxygen at a flow rate of 1 l/min, concentrations of compound A did not increase above those found in the parent drug (1.3-3.3 ppm). In the same experiment, mean +/-SD concentrations of compound A (32.5 +/- 4.5 ppm) were observed when both traditional brands of soda lime were used. After dehydration of the traditional soda limes, immediate exposure to desflurane (60%), enflurane (2%), and isoflurane (2%) produced concentrations of carbon monoxide of 600.0 +/- 10.0 ppm, 580.0 +/- 9.8 ppm, and 620.0 +/-10.1 ppm, respectively. In contrast, concentrations of carbon monoxide were negligible (1-3 ppm) when the anhydrous new absorbent was exposed to the same anesthetics. Conclusions The new material is an effective carbon dioxide absorbent and is chemically unreactive with sevoflurane, enflurane, isoflurane, and desflurane.

Sign in / Sign up

Export Citation Format

Share Document